ANTAGONISM OF THE RESPIRATORY EFFECTS OF ALFENTANIL AND FENTANYL BY NALOXONE IN THE CONSCIOUS RABBIT

The ability of naloxone to antagonize the respiratory effectsof alfentanil, a new short-acting analgesic, was studied inthe rabbit. The results were compared with naloxone antagonismof fentanyl. Minute volume and respiratory frequency, and pH,Pco₂ and standard bicarbonate of arterialized venous blood weremeasured. Naloxone was more effective as an antagonist to alfentanilthan as an antagonist to fentanyl.     

RESPIRATORY EFFECTS OF A NEW OPIATE ANALGESIC, R 39209, IN THE RABBIT: COMPARISON WITH FENTANYL

The respiratory effects of R 39209, a new short-acting analgesic,were studied and compared with those of fentanyl, in the rabbit.Minute volume, respiratory frequency and pH₃ PCO₂ and standardbicarbonate of artcrialized venous blood were measumi R 39209had an earlier peak effect and shorter duration of action thanfentanyl, but otherwise the respiratory effects of the two drugswere similar. Fentanyl was between 2 and 3.5 times more potentthan R 39209. Repeated doses of R 39209 produced reproduciblepeak effects wen when only 10 min was allowed between administranons.     

SEPARATE EFFECTS OF HALOTHANE AND CARBON DIOXIDE ON RESPIRATORY DURATION IN VAGOTOMIZED CATS

The independent effects of halothane and carbon dioxide on centralmechanisms regulating respiratory frequency were investigatedin 12 vagotomized, artificially ventilated cats. Changes inrespiratory pattern analysed from the phrenic neurogram revealedthat increasing Pa_CO2 at a constant depth of halothane anaesthesiacaused a progressive increase in TE with various changes inT1, whereas increasing the depth of halothane anaesthesia ata constant Pa_CO2 caused a progressive decrease in TE with variouschanges in T1. These results suggest that the effect of carbondioxide on central mechanisms regulating respiratory durationis exactly the opposite of that produced by halothane and thatrespiratory frequency is modified by both the depth of halothaneanaesthesia and Pa_CO2.     

EFFECTS OF DOXAPRAM ON POSTOPERATIVE PULMONARY COMPLICATIONS FOLLOWING THORACOTOMY

An i.v. solution of 5% dextrose with doxapram 2 mg ml^–1or 5% dextrose alone was administered to 53 patients followinglateral thoracotomy. Estimations of arterial Po₂ Pco₂ and pHwere made before operation, during infusion and 7 days afteroperation. Respiratory function tests were carried out beforeand 7 days after operation. There were no significant differencesin arterial Po₂ Pco₂ and pH or in respiratory function testsbetween those who received doxapram and those who did not. Inthis study doxapram did not affect the frequency of postoperativepulmonary complications. ^* Present address: Department of Anaesthetics, Wilhelmina Gasthuis,Academisch Ziekenhuis bij de Universiteit van Amsterdam, leHelmersstraat 104, Amsterdam, Holland.     

USE OF VECURONIUM AND DOXAPRAM IN PATIENTS SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA

Neuromuscular blockade was obtained with vecuronium 108 µgkg^–1 in 44 patients under-going diagnostic muscle biopsyas part of an investigation of malignant hyperthermia (MH) susceptibility.At the termination of anaesthesia doxapram 1.43 mg kg^–1was given in an attempt to antagonize postoperative respiratorydepression. Rectal, muscle and skin temperatures, blood lactateconcentration and venous PCO₂ were measured before, during andafter anaesthesia. Susceptibility to MH was established by invitro contracture tests according to the protocol of the EuropeanMH Group. Twenty patients were susceptible to MH (MHS), 19 wereMH nonsusceptible (MHN) and five MH equivocal (MHE). No adverseeffects of the drugs were observed. There were no differencesbetween the three groups in rectal or muscle temperature, bloodlactate concentration or venous PCO₂ at any time. Doxapram didnot prevent an increase in postoperative PCO₂. It is concludedthat vecuronium and doxapram may be safely administered to patientssusceptible to MH.     

CORRELATION OF ALVEOLAR PCO2 ESTIMATED BY INFRA-RED ANALYSIS AND ARTERIAL PCO2 IN THE HUMAN NEONATE AND THE RABBIT

The performance of an infra-red analyser (Beckman LB-2) in samplingalveolar gas at ventilatory frequencies and volumes occuringin the human neonate has been examined. The optimum samplingflow rate was found to be 300 ml/min; at this flow the 90% responsetime of the analyser-catheter system was 140 ms. Correlationof estimated alveolar P2 and arterial PCO₂ was performed inthe rabbit which has a ventilatory rate and tidal volume similarto those of the human neonate. There was a good correlationbetween maximum end-expired PCO₂ (PÉCO₂) and arterialPCO₂ over a wide range of ventilatory rates (10–100 b.p.m.);maximum PÉCO₂ was a better index than mean PÉCO₂or alveolar plateau PÉCO₂     

HAS DROPERIDOL AN ATROPINIC EFFECT?

The action of droperidol on the tachycardia produced by atropineand on the serum concentration of cholinesterases was observedduring balanced anaesthesia. Without atropine, the mean heartrates of patients who received fentanyl or fentanyl plus droperidolwere similar. Atropine increased heart rate only in the presenceof droperidol (P<0.001) (fentanyl v. fentanyl plus droperidol:(P<0.05). Droperidol inhibited serum cholinesterases (P<0.05);this effect was independent of atropine.     

Postoperative analgesia with intravenous fentanyl PCA vs epidural block after thoracoscopic pectus excavatum repair in children

Background: The aim of this prospective, randomized trial was to compareanalgesia, sedation, and cardiorespiratory function in childrenafter thoracoscopic surgery for pectus excavatum repair, usingtwo types of analgesia—epidural block with bupivacaineplus fentanyl vs patient-controlled analgesia (PCA) with fentanyl. Methods: Twenty-eight patients scheduled for thoracoscopic pectus excavatumsurgery were randomly assigned to receive either thoracic epiduralblock or i.v. PCA for postoperative analgesia. Pain was assessedusing a visual-analogue scale (VAS). The Ramsay sedation score,arterial pressure, ventilatory frequency, and heart rate werealso measured, and blood gas analysis was performed regularlyduring the first 48 h after surgery. Results: A significant decrease in the VAS pain score, Ramsay sedationscore, heart rate ventilatory frequency, systolic and diastolicblood pressure, and Pa_CO2, and a significant increase in Pa_O2and oxygen saturation were found over time. Patients in thePCA group had significantly higher Pa_CO2 values. In addition,a significantly slower decline of systolic blood pressure andheart rate, and faster recovery of Pa_CO2 were found in PCA patientsthan in patients with epidural block. Conclusions: I.V. fentanyl PCA is as effective as thoracic epidural for postoperativeanalgesia in children after thoracoscopic pectus excavatum repair.Bearing in mind the possible complications of epidural catheterizationin children, the use of fentanyl PCA is recommended.     

COMPARISON OF THE RESPIRATORY EFFECTS OF ICI 35 868 AND THIOPENTONE IN THE RABBIT

The effects of thiopentone and ICI 35 868 on minute volume,respiratory frequency, tidal volume and arterialized venousPco₂, pH and standard bicarbonate have been compared in therabbit. ICI 35 868 has two to three times the potency of thiopentone,but equivalent anaesthetic doses cause similar decreases inminute volume. ICI 35 868 decreased tidal volume to a greaterextent than thiopentone. Whilst the time courses of the twodrugs were similar in most respects, thiopentone produced amore prolonged increase in Pco₂. This was accompanied by anincrease in standard bicarbonate which was not seen in rabbitstreated with ICI 35 868.     

EFFECT OF HYPERCARBIA ON HEPATIC BLOOD FLOW AND OXYGEN CONSUMPTION IN THE GREYHOUND

The stability of a technique for measuring hepatic blood flowand oxygen consumption was established in six greyhounds anaesthetizedwith pentobarbitone (group A). Subsequently, the effects ofincreased Pa_CO2 were studied in another six animals (group B).With one exception (splenic blood flow) no significant changeswere observed in any of the indices measured in group A. Ingroup B, although hepatic arterial blood flow (HABF) decreasedwhen Pa_CO2 increased, both portal venous blood flow (PVBF) andtotal liver blood flow (HABF + PVBF) increased. However, thesechanges were much less marked after 20 min. Hepatic oxygen consumptionand splenic venous blood flow were unchanged with an increasein Pa_CO2     

Observational study of perioperative PtcCO2 and SpO2 in non-ventilated patients receiving epidural infusion or patient-controlled analgesia using a single earlobe monitor (TOSCA)

Background: TOSCA, a non-invasive monitor with a single earlobe probe incorporatinga Stow–Severinghaus electrode and optical sensor (LindeMedical Sensors AG, Basel, Switzerland), has previously beenused with ventilated patients and in sleep laboratories. Werecorded transcutaneous carbon dioxide pressures (Ptc_CO2) andoxygen saturations (Sp_O2) in non-ventilated patients to investigateopioid-induced respiratory depression. Methods: This observational cohort study included 28 ASA I and II patients,monitored between 10 p.m. and 6 a.m., before and after electivemajor laparotomy. After operation, patients were kept on oxygen,4 litre min^–1, and received either bupivacaine (0.1%)containing fentanyl (2 µg ml^–1) via epidural catheter(epidural analgesia group, EPI; n = 14) or morphine via patient-controlledanalgesia infusion pump (PCA-morphine group, PCA; n = 14). Results: The preoperative median (lower/upper quartile) Ptc_CO2 was similarin both groups at around 5.5 kPa, but significantly higher afteroperation in PCA with 6.9 kPa (5.6/7.3) (P = 0.02), accompaniedby a longer hypercarbia time >6 kPa of 6.6 h (0.1/8.0) (P= 0.04), and lower respiratory rates of 13.9 breaths min^–1(13.3/15.4) (P = 0.04). In EPI, the corresponding results were5.8 kPa (5.5/6.0), 1.2 h (0.1/4.3), and 16.2 breaths min^–1(14.8/16.7). The perioperative median Sp_O2 in both groups wascomparable within the normal range, although generally higherwhen on supplemental oxygen (P = 0.26). The Sp_O2 time <94%was similar in both groups (P = 0.33) as were pain scores (P= 0.25). Conclusions: Ptc_CO2 recording in patients on PCA-morphine and supplementaloxygen revealed hypercapnia in the presence of normal respiratoryrates and Sp_O2 values. This is recommended as an easy and sensitivemonitor of respiratory depression and may have a role in thesafe administration of opioid-analgesia.     

Arterial to end-tidal carbon dioxide tension difference in children with congenital heart disease

In children with congenital cyanotic heart disease, right-to-leftintracardiac shunting causes an obligatory difference betweenarterial and end-tidal carbon dioxide tension (Pa_CO2–PE'_CO2)as venous blood, rich in carbon dioxide, is added to the arterialcirculation. This obligatory Pa_CO2–PE'_CO2 difference,which can be predicted from knowledge of oxygen saturation,haemoglobin concentration and Pa_CO2, increases as oxygen saturationdecreases, most markedly when the haemoglobin concentrationis high. A second possible cause of the Pa_CO2–PE'_CO2 differenceis the effect of pulmonary hypoperfusion caused by the shunt.We studied 60 children undergoing cardiac surgery and comparedthe predicted the Pa_CO2–PE'_CO2 difference with measuredvalues to investigate the extent to which additional factorsinfluence the clinically observed Pa_CO2–PE'_CO2. In manychildren, observed values were much greater than predicted,which is compatible with some degree of pulmonary hypoperfusion.However, this was not felt to represent the complete picturein all patients. Another cause of ventilation–perfusionmismatch was suspected in those children who showed a considerableimprovement in oxygen saturation during ventilation with anincreased FI_O2. We believe that pulmonary congestion causedby large left-to-right shunts may further increase the Pa_CO2–PE'_CO2difference. Br J Anaesth 2001; 86: 349–53     

Gastric mucosal end-tidal PCO2 difference as a continuous indicator of splanchnic perfusion

Gastric mucosal and arterial blood PCO₂ must be known to assessmucosal perfusion by means of gastric tonometry. As end-tidalPCO₂ (PE'_CO2) is a function of arterial PCO₂, the gradient betweenPE'_CO2 and gastric mucosal PCO₂ may reflect mucosal perfusion.We studied the agreement between two methods to monitor gutperfusion. We measured the difference between gastric mucosalPCO₂ (air tonometry) and PE'_CO2 (=DPCO_2gas) and the differencebetween gastric mucosal PCO₂ (saline tonometry) and arterialblood PCO₂ (=DPCO_2sal) in 20 patients with or without lung injury.DPCO_2gas was greater than DPCO_2sal but changes in DPCO_2gas reflectedchanges in DPCO_2sal. The bias between DPCO_2gas and DPCO_2salwas 0.85 kPa and precision 1.25 kPa. The disagreement betweenDPCO_2gas and DPCO_2sal increased with increasing dead space.We propose that the disagreement between the two methods studiedmay not be clinically important and that DPCO_2gas may be a methodfor continuous estimation of splanchnic perfusion. Br J Anaesth 2000; 85: 563–9 ^* Corresponding author: Department of Anesthesiology and IntensiveCare, Division of Critical Care, Kuopio University Hospital,PO Box 1777, FIN-70211 Kuopio, Finland     

Effects of surgical stimulation on the apnoeic thresholds for carbon dioxide during anaesthesia with sevoflurane

Mechanical hyperventilation may produce hypo-capnic apnoea belowthe carbon dioxide off-switch threshold whereas an increasein arterial PCO₂ after post-hyperventilation apnoea causes reappearanceof respiratory effort above the carbon dioxide on-switch threshold.To study the effects of surgical stimulation on these two thresholds,we have measured end-tidal PCO₂ (PE'_CO2) at the two thresholds,before and during surgical stimulation, in 14 patients undergoingmastectomy, anaesthetized with sevoflurane (1.2 MAC). Basedon the reproducibility of the results, data from 11 patientswere analysed and data from the three other patients were discarded.Before surgical stimulation, mean resting P'_CO2, off-switchthreshold and on-switch threshold were 5.7 (SEM 0.2), 5.2 (0.2)and 6.1 (0.2) kPa, respectively. The off-switch threshold wassignificantly less than resting P'_CO2 (P < 0.01) but theon-switch threshold was significantly greater than resting P'_CO2(P < 0.01). During surgical stimulation, resting P'_CO2, off-switchthreshold and on-switch threshold were 4.8 (0.2), 4.1 (0.2)and 4.7 (0.2) kPa, respectively. Although the off-switch thresholdwas significantly less than resting PÉ_CO2, 2 (P <0.01), there were no significant differences between restingP'_CO2 and on-switch threshold. These results indicate that surgicalstimulation does not affect equally the carbon dioxide on- andoff-switch thresholds.     

DOSE-RELATED HAEMODYNAMIC EFFECTS OF CONTINUOUS INFUSIONS OF ALTHESIN IN MAN

The cardiovascular effects of infusions of Althesin at variousrates to supplement nitrous oxide anaesthesia have been studiedin seven spontaneously breathing patients and 11 patients ventilatedartificially to normal Pa_CO2, During spontaneous breathing,increasing rates of Althesin infusion were associated with increasesin heart rate and cardiac output. The modest decrease in arterialpressure ( —5%) was the result of a decrease in vascularresistance. Increasing rates of Althesin infusion were associatedwith increasing values of Pa_CO2 During artificial ventilation,increasing rates of Althesin infusion (up to eight times theminimum infusion rate) caused dose-dependent decreases of arterialpressure and systemic vascular resistance, whereas heart rateand cardiac output were increased slightly at all rates of infusion.     

Pressure-controlled ventilation improves oxygenation during laparoscopic obesity surgery compared with volume-controlled ventilation

Background: We compared pressure and volume-controlled ventilation (PCVand VCV) in morbidly obese patients undergoing laparoscopicgastric banding surgery. Methods: Thirty-six patients, BMI>35 kg m^–2, no major obstructiveor restrictive respiratory disorder, and Pa_CO2<6.0 kPa, wererandomized to receive either VCV or PCV during the surgery.Ventilation settings followed two distinct algorithms aimingto maintain end-tidal CO₂ (E'_CO2) between 4.40 and 4.66 kPaand plateau pressure (P_plateau) as low as possible. Primaryoutcome variable was peroperative P_plateau. Secondary outcomeswere Pa_O2 (FI_O2 at 0.6 in each group) and Pa_CO2 during surgeryand 2 h after extubation. Pressure, flow, and volume time curveswere recorded. Results: There were no significant differences in patient characteristicsand co-morbidity in the two groups. Mean pH, Pa_O2, Sa_O2, andthe Pa_O2/FI_O2 ratio were higher in the PCV group, whereas Pa_CO2and the E'_CO2–Pa_CO2 gradient were lower (all P<0.05).Ventilation variables, including plateau and mean airway pressures,anaesthesia-related variables, and postoperative cardiovascularvariables, blood gases, and morphine requirements after theoperation were similar. Conclusions: The changes in oxygenation can only be explained by an improvementin the lungs ventilation/perfusion ratio. The decelerating inspiratoryflow used in PCV generates higher instantaneous flow peaks andmay allow a better alveolar recruitment. PCV improves oxygenationwithout any side-effects.     

EFFECT OF NALBUPHINE HYDROCHLORIDE ON THE VENTILATORY AND OCCLUSION PRESSURE RESPONSES TO CARBON DIOXIDE IN VOLUNTEERS

We studied the effect of nalbuphine on the ventilatory and occlusionpressure reponses to carbon dioxide rebreathing in six healthymale volunteers (mean age 25.5 yr) in a single-blind laboratorystudy. On four separate days volunteers were assigned randomlyto receive either placebo (0.9% sodium chloride) or three i.v.doses of nalbuphine (15, 30 and 60 mg 70 kg^–1), followed90 min later by naloxone 0.4 mg 70 kg^–1. Duplicate rebreathingtests were performed and the mean intercept at PE'_co2 7 kPaand the slopes of the linear relationship between inspiratoryminute ventilation (Vl) or occlusion pressure (P_0.1) with PE'_co2were measured. Nalbuphine significantly decreased the mean interceptof the Vl (P < 0.01) and P_0.1 (P < 0.05) responses, butcaused no changes in the slopes. No significant difference betweenthe doses was noted, suggesting that an Effect maximum (E'max)for respiratory depression was reached with a dose of approximately15 mg 70 kg^–1. Naloxone was less effective in antagonizingthe depression in Vl at the higher dose of nalbuphine. SimilarP_0.1 values were associated with the same inspiratory flow rate(1 litre s^–1) before and after drug treatment, suggestingthat nalbuphine acts centrally to depress ventilation. Sedationincreased significantly following each dose of nalbuphine (P< 0.001). No demonstrable difference between the doses wasshown, suggesting an Effect maximum (E'max) for sedation wasreached at about 15 mg 70 kg^–1. Administration of nalbuphinewas associated with pain at the injection site, dizziness, dreaming,nausea and vomiting. Cardiovascular stability was maintainedin all subjects.     

DOES A BOLUS OF MANNITOL INITIALLY AGGRAVATE INTRACRANIAL HYPERTENSION?: A Study at Various Paco2 Tensions in Dogs

In two groups of anaesthetized dogs, with (n = 28) or without(n = 28) induced intracranial hypertension, we compared theeffects on intracranial pressure (ICP) of the rapid administrationof mannitol 2 g kg^–1 i.v. at Pa_CO2 2.7, 4.0, 5.3, and6.7 kPa (n = 7). In dogs with no induced intracranial hypertension,ICP increased during the administration of mannitol, reacheda peak at 2 min after infusion, and then gradually decreased(P<0.05). More marked changes in ICP were observed in responseto higher values of Pa_CO2 (P < 0.05). In dogs with inducedintracranial hypertension, the rapid infusion of mannitol causedan exponential decrease in ICP, without initial increase, whichwas significantly steeper at higher values of Pa_CO2 (P <0.05). This was followed by a more gradual decrease which achievedpre-balloon inflation values 10 min after infusion. We postulatethat the absence of the initial increase in ICP is the resultof (1) a concomitant decrease in arterial pressure, (2) a reductionin the volume-pressure response of the brain, (3) the failureof mannitol to dilate further the cerebral arterial vascularbed and (4) a hitherto unnoticed early water-drawing effect.Our study confirmed the safety of rapidly expanding the circulatingblood volume with mannitol in circumstances of increased ICPin dogs. A brief account of this work was presented to the sixth InternationalSymposium on Intracranial Pressure, June 9–, 1985, Glasgow.     

Variation in the arterial to end-tidal Pco2 difference during one-lung thoracic anaesthesia

We have measured the arterial to end-tidal PCO₂ difference (Pa_CO2– PE'_CO2) in 22 patients undergoing pulmonary resectionin the lateral thor-acotomy position during two-lung ventilation(TLV) and after transition to one-lung ventilation (OLV). WithOLV for each patient, the practice of correcting the estimateby an initial measurement of (Pa_CO2 – PE'_CO2) was evaluatedby subtracting the initial (Pa_CO2 – PE'_CO2) from subsequentvalues measured at 10-min intervals. Net (uncorrected) and correcteddifferences during OLV were analysed using ANOVA. (Pa_CO2 –PE'_CO2) values during TLV and OLV were similar: mean (SD) 1.3(0.6) kPa and 1.2 (0.7) kPa, respectively (ns). Mean (Pa_CO2– PE'_CO2) varied in the range 0.2–2.5 kPa, whilemaximum (Pa_CO2 – PE'_CO2) was 0.3–2.8kPa. The mean(SD) of 133 pairs of measurements with OLV was 1.1 (0.7) kPa.Even after correction, mean (Pa_CO2 – PE'_CO2) varied inthe range -0.7 to 0.8 kPa; individual extreme values were from-1.3 to 1.7 kPa. Variation between patients was found to begreater than variation within patients for both net and correcteddifferences (F ratio = 37.0 and 10.9, respectively), althoughcalculating a corrected difference did reduce variation betweenpatients from a mean square value of 2.44 to 0.61. The widevariation in (Pa_CO2 – PE'_CO2) suggests that the accuracyof estimation of Pa_CO2 by monitoring PE'_CO2 although improvedby the use of a corrected difference, remains questionable duringOLV. (Br. J. Anaesth. 1994; 72: 21–24)      

4-AMINOPYRIDINE REVERSAL OF FENTANYL-INDUCED RESPIRATORY DEPRESSION IN NORMOCAPNIC AND HYPERCAPNIC PATIENTS

Profound postoperative respiratory depression after larger dosesof fentanyl was partially reversed by 4-aminopyridine. Thisreversal was independent of FI_O2, suggesting that the responsewas not dependent upon peripheral chemoreceptor-mediated drive.Similar reversal of fentanyl-induced depression by 4-aminopyridinewas observed before surgery in patients breathing 67% nitrousoxide in oxygen. 4-Aminopyridine had no effect on breathingwhen given alone in the absence of fentanyl to patients breathing67% nitrous oxide in oxygen before surgery.